69(P1-17) 活性型ビタミンD_3の立体選択的合成(ポスター発表の部)  [in Japanese] 69(P1-17) STEREOCONTROLLED SYNTEHSIS OF ACTIVE METABOLITES OF VITAMIN D_3  [in Japanese]

An efficient enantiospecific route to the A-ring synthons, 11, 12, and 13 of active metabolites of vitamin D_3 from (R)-(-)-carvone (4) has been developed. The method involves the following major transformations, (i) highly diastereoselective Cr(II)-mediated reaction of the allylic iodide 19 with the aldehyde 20 giving the common precursor 21, (ii) dehydration of 21 under Mitsunobu reaction conditions leading to stereo- and regioselective construction of the requisite diene moiety of 11, (iii) transformation of 21 into the aldehyde 12 through oxidative cleavage of the glycol. A novel enantioselective synthesis of the hidrindanol 29, a C/D-ring synthon for the preparation of vitamin D_3 metabolites, has been achieved starting from cyclopropyl methyl ketone 34. The route relys on stereoselective construction of the hidrindan skeleton by use of newly developed chiral epoxy alcohol-initiated polyolefin cyclization (37→40). The cyclization product 40 was converted into 29 through (i) highly stereoselective introduction of the C-17 side chain by taking advantage of the established methodology involving semihydrogenation, ene reaction, and hydrogenation, (ii) degradative transformation of the C-8 side chain into the hydroxyl group.